Due to the rapidly changing social status and the role of females in the western as well as in developing countries, male contraceptives are greatly in demand. Despite this, no significant progress has been made in the area of male fertility control. This proposal is based on the lead compound, (S)-DHPA, which has shown a remarkable inhibitory activity on spermatogenesis in mice. In order to confirm the activity, the synthesis and tests of (S)-DHPA in rats are proposed. In order to study the structure-activity relationships, (S)-DHPA derivatives containing various purine rings will be synthesized. Further structure activity relationships will be explored with C-nucleoside analogs of (S)-DHPA. The long term objective of this project is to develop a clinically safe, effective, and reversible male contraceptive.